tbuckley/cabot-search huggingface dataset:
Understanding Infection Risk with Anti-BCMA Bispecific Antibodies
Authors: Alfred L. Garfall, Edward A. Stadtmauer
Journal: Blood Cancer Discovery (2023)

Summary: Lancman and colleagues find that infection risk in patients treated with anti-BCMA bispecific antibodies for relapsed/refractory multiple myeloma is associated with severe immunoglobulin deficiency and may be mitigated by immunoglobulin replacement therapy. The study has implications for managing infection risk and raises questions about the optimal duration of treatment with these potent, novel immunotherapies. See related article by Lancman et al., p. 440 (4) .
Issue Information
Journal: Arthritis & Rheumatology (2023)

Arthritis & RheumatologyVolume 75, Issue 10 Issue InformationFree Access Issue Information First published: 28 September 2023 https://doi.org/10.1002/art.42221AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume75, Issue10October 2023 RelatedInformation
In This Issue
Journal: Arthritis & Rheumatology (2023)

Individual gut microbiota alterations local mucosa immunity status.Such physical barrier also likely boost the exposure of bacterial antigens at the mucosal interface and subsequently activate the intestinal immune response.Moreover, in the case of rheumatoid arthritis (RA), animal models of arthritis have demonstrated that microbiota can drive RA pathogenesis.In this issue, Luo et al (p.1736) report that gut microbial and metabolome alterations are common in individuals at high risk for RA.In addition, fecal microbiota transplantation (FMT) from these preclinical individuals into mice triggered intestinal barrier dysfunction and changes in mucosal immunity, which contributed to the development of arthritis.Their study included anti-citrullinated protein antibody-positive, high-risk individmented that stool microbial diversity was lower in PreRA individuals than in healthy controls (HC).Moreover, the bacterial community structure and function differed significantly between PreRA individuals and HCs.For example, in the feces of the PreRA populations, the relative abundance p. 1736
Impact of venous thromboembolism on the mortality in patients with cancer: a population-based cohort study
Authors: Henrik Toft Sørensen, Lars Pedersen, Nick van Es, Harry R. Büller, Erzsébet Horváth-Puhó
Journal: The Lancet Regional Health - Europe (2023)

Despite recent improvements in the treatment of cancer, little is known about the long-term survival in patients with cancer and venous thromboembolism. We aimed to examine the five-year mortality of venous thromboembolism in cancer patients in a large population-based cohort study.Using Danish healthcare registries from 1995 to 2020, we obtained data on cancer patients with venous thromboembolism and comparison cohorts of cancer patients without venous thromboembolism, matched in terms of cancer type, age, sex, and year of cancer diagnosis, and adjusted for level of comorbidity and frailty using the Charlson Comorbidity Index Score and Hospital Frailty Risk Score, marital status, use of selected medications, and recent surgery (<90 days).During the study period, 886,536 patients were diagnosed with cancer. Of 1882 cancer patients diagnosed at the time of their venous thromboembolism, 44.4% (835/1882) had distant metastases. In this cohort, the one- and five-year mortality cumulative incidences were 68% (1284/1882) and 84% (1578/1882), respectively, in contrast to 38% (2135/5549) and 67% (3653/5549) in the comparison cohort. The mortality rate ratio was 4.34 (95% confidence interval [CI], 3.95-4.78) for the first year of follow-up and 3.44 (95% CI 3.17-3.73) for the five-year follow-up period. Of the 23,366 patients diagnosed with venous thromboembolism after cancer diagnosis, 18% (4183/23,366) had distant metastases at the time of cancer diagnosis. The cumulative incidence of death at one year was 45% (10,465/23,366; mortality rate ratio 3.48, 95% CI 3.37-3.60) and at five years 69% (15,669/23,366; mortality rate ratio 2.57, 95% CI 2.50-2.63).Despite improved cancer treatment, venous thromboembolism in cancer patients is strongly associated with a poor prognosis.The study was supported by grants from the Independent Research Fund Denmark (record no. 3101-00102B) and the Karen Elise Jensen Foundation.
<i>FGFR3</i> Alterations in Bladder Cancer Stimulate Serine Synthesis to Induce Immune-Inert Macrophages That Suppress T-cell Recruitment and Activation
Authors: Yi Ouyang, Ziwei Ou, Wenlong Zhong, Jin Yang, Sha Fu, Nengtai Ouyang, Junyu Chen, Longhao Xu, Daqin Wu, Junan Qian, Yi Lin, Tianxin Lin, Jian Huang
Journal: Cancer Research (2023)

Abstract FGFR3 alterations are common in patients with bladder cancer. While the FGFR tyrosine kinase inhibitor erdafitinib has been approved as a targeted therapy for patients with FGFR3-altered (aFGFR3) bladder cancer, the response rate remains suboptimal, prompting development of strategies to improve treatment response. Here, we observed an immune-desert tumor microenvironment (TME) phenotype in human aFGFR3 bladder cancer and demonstrated that mutant FGFR3 indirectly induces a “cold” TME in mouse bladder cancer models. Single-cell RNA sequencing revealed the central role of macrophages in inducing the cold TME of aFGFR3 tumors. Macrophages in aFGFR3 tumors exhibited reduced T-cell recruitment and antigen presentation capabilities. Increased serine synthesis in bladder cancer cells that was induced by mutant FGFR3 activated the PI3K/Akt pathway in macrophages, shifting them to an immune-inert phenotype. Targeting PI3K in aFGFR3 tumors with duvelisib achieved promising efficacy by reversing the macrophage phenotype, and combination therapy with duvelisib and erdafitinib demonstrated increased antitumor activity. Overall, these findings reveal the critical role of enhanced serine synthesis efflux from cancer cells with mutant FGFR3 in shifting macrophages to an immune-inert phenotype. Reversing the macrophage phenotype holds promise for enhancing erdafitinib efficacy. Significance: Metabolic reprogramming of bladder cancer cells driven by mutant FGFR3 increases serine synthesis that suppresses macrophage immunostimulatory functions to generate an immunosuppressive TME, which can be overcome by targeting PI3K.
Health experts call for a “feminist approach” to cancer care
Authors: Jacqui Wise
Journal: BMJ (2023)

Health experts call for a "feminist approach" to cancer care Jacqui WiseGender inequalities significantly worsen women's access to cancer prevention, care, and treatment, say health experts who are calling for the immediate introduction of a "feminist approach" to cancer.A Lancet Commission on women, power, and cancer says that the cancer burden in women is significantly under-recognised with cancer ranking in the top three causes of premature mortality among women in almost all countries worldwide.
Immunological factors linked to geographical variation in vaccine responses
Authors: Marloes M. A. R. van Dorst, Jeremia J. Pyuza, Gyaviira Nkurunungi, Vesla I. Kullaya, Hermelijn H. Smits, Pancras C. W. Hogendoorn, Linda J. Wammes, Bart Everts, Alison M. Elliott, Simon P. Jochems, Maria Yazdanbakhsh
Journal: Nature reviews. Immunology (2023)
Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial
Authors: Maja Di Rocco, Eduardo Forleo-Neto, Robert J. Pignolo, Richard Keen, Philippe Orcel, Thomas Funck-Brentano, Christian Roux, Sami Kolta, Annalisa Madeo, Judith S. Bubbear, Jacek Tabarkiewicz, Małgorzata Szczepanek, Javier Bachiller-Corral, Angela M. Cheung, Kathryn M. Dahir, Esmée Botman, Pieter G. Raijmakers, Mona Al Mukaddam, Lianne Tile, Cynthia Portal-Celhay, Neena Sarkar, Peijie Hou, Bret J. Musser, Anita Boyapati, Kusha Mohammadi, Scott J. Mellis, Andrew J. Rankin, Aris N. Economides, Dinko Gonzalez Trotter, Gary A. Herman, Sarah J. O’Meara, Richard DelGizzi, David M. Weinreich, George D. Yancopoulos, E. Marelise W. Eekhoff, Frederick S. Kaplan
Journal: Nature Medicine (2023)

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET-CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .
Molecular classification of hormone receptor-positive HER2-negative breast cancer
Authors: Xi Jin, Yi-Fan Zhou, Ding Ma, Shen Zhao, Cai-Jin Lin, Yi Xiao, Tong Fu, Cheng-Lin Liu, Yi-Yu Chen, Wen-Xuan Xiao, Ya-Qing Liu, Qing-Wang Chen, Ying Yu, Le-Ming Shi, Jin-Xiu Shi, Wei Huang, John F. R. Robertson, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Nature Genetics (2023)
Tom Nolan’s research reviews—28 September 2023
Authors: Tom Nolan
Journal: BMJ (2023)

Surrey Goodnight for overnight appendicectomyHow long should people with appendicitis wait before going to theatre? 1822 people with presumed uncomplicated appendicitis admitted to hospital in Norway and Finland were randomised to have an appendicectomy either within 8 hours (which might mean operating overnight) or within 24 hours.There was no statistically significant difference in rates of perforation at appendicectomy between the two groups (8% and 9% respectively) or in outcomes at 30 days.The findings suggest that those with uncomplicated appendicitis-which in this study meant excluding people with a C reactive protein level of ≥100 mg/L, fever >38.5°C, signs of complicated appendicitis on imaging studies, or generalised peritonitis-can probably wait until morning.
In-ear integrated sensor array for the continuous monitoring of brain activity and of lactate in sweat
Authors: Yuchen Xu, Ernesto De la Paz, Akshay Paul, Kuldeep Mahato, Juliane R. Sempionatto, Nicholas Tostado, Min Lee, Gopabandhu Hota, Muyang Lin, Abhinav Uppal, William Chen, Srishty Dua, Lu Yin, Brian L. Wuerstle, Stephen Deiss, Patrick Mercier, Sheng Xu, Joseph Wang, Gert Cauwenberghs
Journal: Nature Biomedical Engineering (2023)

Owing to the proximity of the ear canal to the central nervous system, in-ear electrophysiological systems can be used to unobtrusively monitor brain states. Here, by taking advantage of the ear's exocrine sweat glands, we describe an in-ear integrated array of electrochemical and electrophysiological sensors placed on a flexible substrate surrounding a user-generic earphone for the simultaneous monitoring of lactate concentration and brain states via electroencephalography, electrooculography and electrodermal activity. In volunteers performing an acute bout of exercise, the device detected elevated lactate levels in sweat concurrently with the modulation of brain activity across all electroencephalography frequency bands. Simultaneous and continuous unobtrusive in-ear monitoring of metabolic biomarkers and brain electrophysiology may allow for the discovery of dynamic and synergetic interactions between brain and body biomarkers in real-world settings for long-term health monitoring or for the detection or monitoring of neurodegenerative diseases.
Enzyme-mediated depletion of methylthioadenosine restores T cell function in MTAP-deficient tumors and reverses immunotherapy resistance
Authors: Donjeta Gjuka, Elio Adib, Kendra Garrison, Jianfeng Chen, Yuxue Zhang, Wenjiao Li, Daniel Boutz, Candice Lamb, Yuri Tanno, Amin Nassar, Talal El Zarif, Neil Kale, Mehrdad Rakaee, Tarek H. Mouhieddine, Sarah Abou Alaiwi, Alexander Gusev, Thomas Rogers, Jianjun Gao, George Georgiou, David J. Kwiatkowski, Everett Stone
Journal: Cancer Cell (2023)
Differences in hospital admissions for acute exacerbations of COPD during the COVID-19 pandemic stratified by stable-state blood eosinophil count
Authors: Hnin Aung, Hamish McAuley, Kate Porter, Matthew Richardson, Adam Wright, Christopher E. Brightling, Neil J. Greening
Journal: European Respiratory Journal (2023)

Acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) are driven through different triggers, including infection such as viruses and bacteria. However, nearly 40% of exacerbations are associated with a blood eosinophilia and related to type 2 inflammation (T2High) [1]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: H. Aung, H. McAuley, K. Porter and M.Richardson have nothing to disclose Conflict of Interest: A. Wright's Institute have received grant income from Sanofi. Conflict of Interest: C.Brightling has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. Conflict of Interest: N.Greening has received honoraria for lectures, conference travel and advisory boards from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKleine and Pulmonx. His institute have received grants and consultation fees from Genentech, Roche and GlaxoSmithKline.
Loss of p53 and mutational heterogeneity drives immune resistance in an autochthonous mouse lung cancer model with high tumor mutational burden
Authors: Mingrui Zhu, Jiwoong Kim, Qing Deng, Biagio Ricciuti, Joao V. Alessi, Buse Eglenen-Polat, Matthew E. Bender, Hai-Cheng Huang, Ryan R. Kowash, Ileana Cuevas, Zachary T. Bennett, Jinming Gao, John D. Minna, Diego H. Castrillon, Mark M. Awad, Lin Xu, Esra A. Akbay
Journal: Cancer Cell (2023)
Shared GABA transmission pathology in dopamine agonist- and antagonist-induced dyskinesia
Authors: Yoshifumi Abe, Sho Yagishita, Hiromi Sano, Yuki Sugiura, Masanori Dantsuji, Toru Suzuki, Ayako Mochizuki, Daisuke Yoshimaru, Junichi Hata, Mami Matsumoto, Shu Taira, Hiroyoshi Takeuchi, Hideyuki Okano, Nobuhiko Ohno, Makoto Suematsu, Tomio Inoue, Atsushi Nambu, Masahiko Watanabe, Kenji F. Tanaka
Journal: Cell Reports Medicine (2023)

Dyskinesia is involuntary movement caused by long-term medication with dopamine-related agents: the dopamine agonist 3,4-dihydroxy-L-phenylalanine (L-DOPA) to treat Parkinson's disease (L-DOPA-induced dyskinesia [LID]) or dopamine antagonists to treat schizophrenia (tardive dyskinesia [TD]). However, it remains unknown why distinct types of medications for distinct neuropsychiatric disorders induce similar involuntary movements. Here, we search for a shared structural footprint using magnetic resonance imaging-based macroscopic screening and super-resolution microscopy-based microscopic identification. We identify the enlarged axon terminals of striatal medium spiny neurons in LID and TD model mice. Striatal overexpression of the vesicular gamma-aminobutyric acid transporter (VGAT) is necessary and sufficient for modeling these structural changes; VGAT levels gate the functional and behavioral alterations in dyskinesia models. Our findings indicate that lowered type 2 dopamine receptor signaling with repetitive dopamine fluctuations is a common cause of VGAT overexpression and late-onset dyskinesia formation and that reducing dopamine fluctuation rescues dyskinesia pathology via VGAT downregulation.
Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma
Authors: Meijie Tian, Jun S. Wei, Nityashree Shivaprasad, Steven L. Highfill, Berkley E. Gryder, David Milewski, G. Tom Brown, Larry Moses, Hannah Song, Jerry T. Wu, Peter Azorsa, Jeetendra Kumar, Dina Schneider, Hsien-Chao Chou, Young K. Song, Abdelrahman Rahmy, Katherine E. Masih, Yong Yean Kim, Brian Belyea, Corinne M. Linardic, Boro Dropulic, Peter M. Sullivan, Poul H. Sorensen, Dimiter S. Dimitrov, John M. Maris, Crystal L. Mackall, Rimas J. Orentas, Adam T. Cheuk, Javed Khan
Journal: Cell Reports Medicine (2023)

Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS. The 3A11 CAR T cells induced robust cytokine production and cytotoxicity against RMS cell lines in vitro. In contrast, a panel of healthy human primary cells failed to activate 3A11 CAR T cells, confirming the selectivity of 3A11 CAR T cells against tumors with high FGFR4 expression. Finally, we demonstrate that 3A11 CAR T cells are persistent in vivo and can effectively eliminate RMS tumors in two metastatic and two orthotopic models. Therefore, our study credentials CAR T cell therapy targeting FGFR4 to treat patients with RMS.
Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial
Authors: Mu-Chen Zhang, Shuang Tian, Di Fu, Li Wang, Shu Cheng, Hong-Mei Yi, Xu-Feng Jiang, Qi Song, Yan Zhao, Yang He, Jian-Feng Li, Rong-Ji Mu, Hai Fang, Hao Yu, Hui Xiong, Biao Li, Sai-Juan Chen, Peng-Peng Xu, Wei-Li Zhao
Journal: Cancer Cell (2023)

We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs. 73% (p = 0.005). Two-year progression-free survival rates were 88% vs. 63% (p < 0.001), and 2-year overall survival rates were 94% vs. 77% (p = 0.001). Meanwhile, post hoc RNA-sequencing validated our simplified genetic subtyping algorithm and previously established lymphoma microenvironment subtypes. Our findings highlight the efficacy and safety of R-CHOP-X, a mechanism-based tailored therapy, which dually targeted genetic and microenvironmental alterations in patients with newly diagnosed DLBCL.
Tackling climate change: the pivotal role of clinicians
Authors: Jeffrey Braithwaite, Anuradha Pichumani, Philip Crowley
Journal: BMJ (2023)

### What you need to know ### Sources and selection criteria We searched Medline for articles, and the internet for publicly available reports of policy actions by healthcare services and institutions seeking to limit their greenhouse gas emissions. We also drew on our own expertise. Every healthcare professional, manager, policymaker, politician, and patient has a role to play in securing net zero carbon emissions in healthcare, and front line clinicians can make a profound difference. This article offers an overview of the carbon footprint of healthcare, as a preview to the BMJ's Actions for Sustainable Healthcare series, which will highlight practical actions clinicians can take to support reaching the net zero goal. Key terms used in this article are defined in box 1. Box 1 ### Definitions of key terms 1 - 8 RETURN TO TEXT
Influenza, Tdap, and COVID-19 Vaccination Coverage and Hesitancy Among Pregnant Women — United States, April 2023
Authors: Hilda Razzaghi, Katherine E. Kahn, Kayla Calhoun, Emma Garacci, Tami H. Skoff, Sascha R. Ellington, Tara C. Jatlaoui, Carla L. Black
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines can reduce the risk for influenza, pertussis, and COVID-19 among pregnant women and their infants. To assess influenza, Tdap, and COVID-19 vaccination coverage among women pregnant during the 2022-23 influenza season, CDC analyzed data from an Internet panel survey conducted during March 28-April 16, 2023. Among 1,814 survey respondents who were pregnant at any time during October 2022-January 2023, 47.2% reported receiving influenza vaccine before or during their pregnancy. Among 776 respondents with a live birth by their survey date, 55.4% reported receiving Tdap vaccine during pregnancy. Among 1,252 women pregnant at the time of the survey, 27.3% reported receipt of a COVID-19 bivalent booster dose before or during the current pregnancy. Data from the same questions included in surveys conducted during influenza seasons 2019-20 through 2022-23 show that the proportion of pregnant women who reported being very hesitant about influenza and Tdap vaccinations during pregnancy increased from 2019-20 to 2022-23. Pregnant women who received a provider recommendation for vaccination were less hesitant about influenza and Tdap vaccines. Promotion of efforts to improve vaccination coverage among pregnant women, such as provider recommendation for vaccination and informative conversations with patients to address vaccine hesitancy, might reduce vaccine hesitancy and increase coverage with these important vaccines to protect mothers and their infants against severe respiratory diseases.